Impurities in pharmaceuticals are the unwanted chemicals that remain with the
active pharmaceutical ingredient (API), or develop during formulation, or upon aging
of both API and formulated products. Th e presence of these unwanted chemicals even
in small amounts may infl uence the effi cacy and safety of the pharmaceutical products.
According to the International Conference on Harmonization (ICH) of Technical
Requirements for Registration of Pharmaceuticals for Human Use, impurities
are classifi ed as organic impurities, inorganic impurities and residual solvents. Impurities
can originate from several sources, such as starting materials, synthetic intermediates
and by-products, degradation products arising during storage, functional
group-related typical degradation, mutual interaction amongst ingredients and formulation-
related impurities. Control of stereochemical purity of an API with chiral
centers is also necessary. Also, polymorphic forms are sometimes considered as impurities
that need to be controlled.
Impurity profi ling is the common name of a group of analytical activities, the
aim of which is the detection, identifi cation/structure elucidation and quantitative
determination of organic and inorganic impurities, as well as residual solvents in bulk
drugs and pharmaceutical formulations. Since this is the best way to characterize the
quality and stability of bulk drugs and pharmaceutical formulations, this is the core
activity in modern drug analysis. Highly sophisticated analytical techniques, such as
chromatographic, spectroscopic and hyphenated techniques, are inevitable tools in
the detection, identification, characterization and quantification of impurities.